Liver function as an engineering system

Abstract

Process Systems Engineering has tackled a wide range of problems including manufacturing, the environment, and advanced materials design. Here we discuss how tools can be deployed to tackle medical problems which involve complex chemical transformations and spatial phenomena looking in particular at the liver system, the body's chemical factory. We show how an existing model has been developed to model distributed behavior necessary to predict the behavior of drugs for treating liver disease. The model has been used to predict the effects of suppression of de novo lipogenesis, stimulation of b-oxidation and a combination of the two. A reduced model has also been used to explore the prediction of behavior of hormones in the blood stream controlling glucose levels to ensure that levels are kept within safe bounds using interval methods. The predictions are made resulting from uncertainty in two key parameters with oscillating input resulting from regular feeding. V C 2016 The Authors AIChE Journal published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers AIChE J, 62: 3285-3297, 2016 Keywords: mathematical modeling, biomedical engineering, systems biology, medical, controlThe liver, its regulation, and its diseases Why systems engineering of the liver?Systems Engineering is the discipline of the management of complex engineering systems over their whole life cycle. Process Systems Engineering is the study of complex process engineering systems involving chemical and physical change. Prof Roger Sargent was a pioneer from the 1950s in seeing the potential that computers could have to revolutionize the way that we tackled these problems.1 He also saw the way Chemical Engineering was broadening its base into molecular and biological systems to improve manufacturing. 1,2The liver is one part of a very complex processing system which ensures that all parts of the body receive the energy and nutrients that they need, that waste products are removed efficiently from the various streams, and that short and long term well being are maintained. It is the body's central chemical processing organ. Considering the liver system as one which controls chemical and physical change within the body, particularly of nutrition, makes it a legitimate area of study for Process Systems Engineers. A number of Chemical Engineers have also contributed to the use for Process Systems Engineering to a range of medical applications. Bogle 3 reviews recent

Liver Bioreactor Design Issues of Fluid Flow and Zonation, Fibrosis, and Mechanics: A Computational Perspective

“…Hijmans et al [176] conducted a review of the consequences of combined glucose and fatty acid zonation for insulin resistance, steatosis, and non-alcoholic fatty liver disease. These observations were quantified more completely in work by Ashworth et al [177,178], who developed a 1D zoned eight-compartment model of the liver lobule with detailed kinetics. This extensive model considered approximately 20 components and reactions, as well as protocols for adjusting feeding schedules.…”

Computational Modeling in Liver Surgery

“…Computational models of central liver functions have been developed, e.g., for the hepatic glucose homeostasis (König et al, 2012 ) providing insights into the switch of glucose pathways and the role of hormonal regulation. Additional examples are a minimal model of lipid metabolism in steatosis development (Schleicher et al, 2014 ) and a computational model of both hepatic glucose and lipid metabolism (Ashworth W. B. et al, 2016 ; Ashworth W. et al, 2016 ) yielding insight in the development of steatosis. Moreover, one possible mechanism involved in hepatic lipid deficiencies was elucidated by a detailed kinetic model of fatty acid beta-oxidation, in which an overload of substrate slowed down lipid degradation (van Eunen et al, 2013 ).…”

“…One common approach of coupling metabolism to perfusion is treating the 1D porto-central axis of the sinusoid, consisting of a sinusoid surrounded by hepatocytes, as the repeating unit of the liver. Such ODE-based computational models were used to model the zonated damage and steatosis in NAFLD (Ashworth W. et al, 2016 ) or to analyze glucose homeostasis (Chalhoub et al, 2007 ; Ashworth W. B. et al, 2016 ), lipid metabolism (Schleicher et al, 2014 , 2017 ), hepatic glucose and lipid metabolism (Chalhoub et al, 2007 ), the detoxification of xenobiotics like acetaminophen (Sluka et al, 2016 ), or effects of zonated damage on drug metabolism (Schwen et al, 2015 , 2016 ). These sinusoidal unit models can be used as building blocks of whole-liver and whole-body models (for details, cf.…”